Inheritability of Exon Expression Alterations In Schizophrenia

M. P. Vawter; P. A. Sequeira; B. Rollins
International Congress on Schizophrenic Research. 2007.


Gene expression is a quantitative trait with a strong heritable component as reported in recent yeast, mice, maize, and human studies. The study of transcriptome regulation of individual transcripts has previously focused on cis-regulatory effects. Loci with large trans-regulatory effects might be an important mechanism for transcript alteration in schizophrenia 1. Here we present evidence of exon-specific expression alterations in schizophrenia using a screen of 1.4 million putative exons and a mapping of strong trans- and cis-regulatory loci for these exons. We studied lymphoblastic cell lines under two environmental conditions to measure the effects of stress on the exon expression in these cell lines of 4 families with schizophrenia matched for gender and age to unaffected members. We measured linkage to cis- and trans- regulatory loci of exon expression quantitative traits using a microsatellite marker scan and a previously described method 1. We present evidence that: 1) specific exon expression alterations in schizophrenia are linked to cis- and trans- regulatory loci, 2) exons containing SNPs hybridize differentially to Affymetrix probes which suggests that allelic expression may be detected with the exon array platform, and 3) differential exon expression in schizophrenia occurs in the absence of overall transcript expression differences. Exon expression patterns present an interesting variant of an expression phenotype to study cis and trans regulatory loci in schizophrenia and other complex disorders. 1 Vawter, MP et al. (2006). Genome scans and gene expression microarrays converge to identify gene regulatory loci relevant in schizophren.